The spiny mouse, Acomys cahirinus, is an adult mammal capable of remarkable feats of scar-free tissue regeneration after damage to several organs including the skin and the heart. Here we investigate the regenerative properties of the skeletal muscle of A. cahirinus tibialis anterior in comparison to the lab mouse, Mus musculus. The A. cahirinus TA showed a similar distribution of myosin heavy chain fibre types and a reduced proportion of oxidative fibres compared to M. musculus. There were differences in the matrix components of the TA with regard to collagen VI and the biomechanical properties. A. cahirinus TA regenerated faster with a more rapid induction of embryonic myosin and higher levels of dystrophin than in M. musculus fibres. There were lower levels of inflammation (NF-kB), fibrosis (TGFβ-1, collagens) and higher levels of the anti-inflammatory cytokine Cxcl12. There was a difference in macrophage profile between the two species. After multiple rounds of muscle regeneration the M. musculus TA failed to regenerate muscle fibres and instead produced a large numbers of adipocytes whereas the A. cahirinus TA regenerated perfectly. This clearly improved regeneration performance can be explained by differing levels of growth factors such as adiponectin between the two species.